Metal induced conformational changes in human insulin: Crystal structures of Sr²⁺, Ni²⁺ and Cu²⁺ Complexes of human insulin

Crystal structures of Sr²⁺, Ni²⁺ and Cu²⁺ of human insulin complexes have been determined. The structures of Sr ²⁺ and Ni²⁺ complexes are similar to Zn²⁺ insulin and are in T6 conformation. (All the six monomers in the insulin hexamer are in Tensed conformation (T), which means the first eight residues of B-chain are in an extended conformation). Cu²⁺ complex, though it assumes T6 conformation, has more structural differences due to lowering of crystal symmetry and space group shift from H3 (Hexagonal crystal system) to P3 (Trigonal crystal system) and a doubling of the c axis. 2Ni²⁺ human insulin when compared to 4Ni²⁺ Arg insulin suggests that terminal modifications may be responsible for additional metal binding. All the three metals have been shown to have a role in diabetes and hence may be therapeutically useful.